Factive

Factive

gemifloxacin

Manufacturer:

LG Chem Life Sciences

Distributor:

DKSH
Full Prescribing Info
Contents
Gemifloxacin mesylate.
Description
Gemifloxacin mesylate 426.39 mg equivalent to gemifloxacin 320 mg.
Action
ATC Code: J01MA fluoroquinolone class.
Pharmacology: Pharmacodynamics: General Properties: Gemifloxacin is a synthetic antibacterial agent. Gemifloxacin is a fluoroquinolone antibiotic with a wide range of Gram-positive and Gram-negative pathogens.
Mode of Action: The mode of action is by inhibiting DNA synthesis through the inhibition of both bacterial DNA gyrase and topoisomerase. Gemifloxacin is highly selective for bacterial rather than human topoisomerase II, having strong affinity for bacterial topoisomerases II (DNA gyrase) and IV, which are essential enzymes that play a decisive part in the replication, transcription and repair of bacterial DNA.
Gemifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the Indications & Dosage & Administration.
Susceptible Microorganisms: Aerobic Gram-positive: Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP])*
*MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥2 µg/mL), 2nd generation cephalosporins (e.g., cefuroxirne), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
Aerobic Gram-negative: Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae ( many strains are only moderately susceptible), Moraxella catarrhalis.
Other microorganisms: Chlamydia pneumoniae, Mycoplasma pneumoniae
The following data are available, but their clinical significance is unknown. Gemifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 0.25 µg/mL or less against most (90%) strains of the following microorganisms; however, the safety and effectiveness of gemifloxacin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials: Aerobic gram-positive microorganisms: Staphylococcus aureus (methicillin-susceptible strains only), Streptococcus pyogenes.
Aerobic gram-negative microorganisms: Acinetobacter lwoffii, Klebsiella oxytoca, Legionella pneumophila, Proteus vulgaris.
Pharmacokinetics: The pharmacokinetics of gemifloxacin are approximately linear over the dose range from 40 mg to 640 mg. There was minimal accumulation of gemifloxacin following multiple oral doses up to 640 mg a day for 7 days (mean accumulation <20%). Following repeat oral administration of 320 mg gemifloxacin once daily, steady-state is achieved by the third day of dosing.
Absorption and Bioavailability: Gemifloxacin, given as an oral tablet, is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations of gemifloxacin were observed between 0.5 and 2 hours following oral tablet administration and the absolute bioavailability of the 320 mg tablet averaged approximately 71% (95% CI 60%- 84%). Following repeat oral doses of 320 mg to healthy subjects, the mean± SD maximal gemifloxacin plasma concentrations (Cmax) and systemic drug exposure (AUC (0-24)) were 1.61 ± 0.51 µg/mL (range 0.70-2.62 tg/mL) and 9.93 ± 3.07 µg•hr/mL (range 4.71-20.1 µg•hr/mL), respectively. In patients with respiratory and urinary tract infections (n=1423), similar estimates of systemic drug exposure were determined using a population pharmacokinetics analysis (geometric mean AUC (0-24), 8.36 µg•hr/mL; range 3.2 - 47.7 µg•hr/mL. The pharmacokinetics of gemifloxacin were not significantly altered when a 320 mg dose was administered with a high-fat meal. Therefore Factive tablets may be administered without regard to meals.
Distribution: In vitro binding of gemifloxacin to plasma proteins in healthy subjects is approximately 60 to 70% and is concentration independent. After repeated doses, the in vivo plasma protein binding in healthy elderly and young subjects ranged from 55% to 73% and was unaffected by age. Renal impairment does not significantly affect the protein binding of gemifloxacin. The blood-to-plasma concentration ratio of gemifloxacin was 1.2:1. The geometric mean for Vdss/F is 4.18 L/kg (range, 1.66 - 12.12 L/kg). Gemifloxacin is widely distributed throughout the body after oral administration. Concentrations of gemifloxacin in bronchoalveolar lavage fluid exceed those in the plasma. Gemifloxacin penetrates well into lung tissue and fluids. After five daily doses of 320 mg gemifloxacin, concentrations in plasma, bronchoalveolar macrophages, epithelial lining fluid and bronchial mucosa at approximately 2 hours are indicated in table as follows. (See Table 1.)

Click on icon to see table/diagram/image

Metabolism: Gemifloxacin is metabolized to a limited extent by the liver. The unchanged compound is the predominant drug-related component detected in plasma (approximately 65%) up to 4 hours after dosing. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin. Cytochrome P450 enzymes do not play an important role in gemifloxacin metabolism, and the metabolic activity of these enzymes is not significantly inhibited by gemifloxacin.
Elimination: Gemifloxacin and its metabolites are excreted via dual routes of excretion. Following oral administration of gemifloxacin to healthy subjects, a mean (± SD) of 61 ± 9.5% of the dose was excreted in the feces and 36 ± 9.3% in the urine as unchanged drug and metabolites. The mean (± SD) renal clearance following repeat doses of 320 mg was approximately 11.6 ± 3.9 L/hr (range 4.6-17.6 L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin. The mean (± SD) plasma elimination half-life at steady state following 320 mg to healthy subjects was approximately 7 ± 2 hours (range 4-12 hours).
Special Population: Geriatric: In adult subjects, the pharmacokinetics of gemifloxacin are not affected by age.
Gender: There are no significant differences between gemifloxacin pharmacokinetics in males and females when differences in body weight are taken into account. Population pharmacokinetic studies indicated that following administration of 320 mg gemifloxacin, AUC values were approximately 10% higher in healthy female patients compared to males. No gemifloxacin dosage adjustment based on gender is necessary.
Renal Insufficiency: Results from population pharmacokinetic and clinical pharmacology studies with repeated 320 mg doses indicate the clearance of gemifloxacin is reduced and the plasma elimination is prolonged, leading to an average increase in AUC values of approximately 70% in patients with renal insufficiency. In the pharmacokinetic studies, gemifloxacin Cmax was not significantly altered in subjects with renal insufficiency. Dose adjustment in patients with creatinine clearance ≥40 mL/min is not required. Modification of the dosage is recommended for patients with creatinine clearance <40 mL/min.
Hepatic Insufficiency: The pharmacokinetics following a single 320 mg dose of gemifloxacin were studied in patients with mild to severe hepatic impairments. There was a mean increase in AUC and in Cmax in these subjects with hepatic impairment compared to healthy volunteers. These average pharmacokinetic increases are not considered to be clinically significant. There was no significant change in plasma elimination half-life in the mild, moderate or severe hepatic impairment patients. No dosage adjustment is recommended in patients with mild, moderate or severe hepatic impairment(Child-Pugh A, B and C).
Indications/Uses
FACTIVE is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed as follows.
Acute bacterial exacerbation of chronic bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.
Because fluoroquinolones, including FACTIVE, have been associated with serious adverse reactions (see Warnings) and for some patients ABECB is self-limiting, reserve FACTIVE for treatment of ABECB in patients who have no alternative treatment options.
Community-acquired pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae (including multidrug resistant strains [MDRSP]) *, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae.
*MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin, 2nd generation cephalosporins, e.g. cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of FACTIVE and other antibacterial drugs, FACTIVE should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage/Direction for Use
FACTIVE can be taken with or without food and should be swallowed whole with a liberal amount of liquid. The recommended dose of FACTIVE is 320 mg daily, according to the following table. (See Table 2.)
Table of the clinical decision regarding the use of a 5 or 7 day regimen should be guided by results of the initial sputum culture.

Click on icon to see table/diagram/image

Mode of Administration: Factive can be taken with or without food and should be swallowed whole with a liberal amount of liquid. The recommended dose of Factive is 320 mg daily, according to following indication.

Click on icon to see table/diagram/image
Overdosage
In the event of acute oral overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage; the patient should be carefully observed and treated symptomatically. Adequate hydration should be maintained and hemodialysis does not remove gemifloxacin sufficiently to be useful in overdosage. No specific antidote is known.
Contraindications
Known hypersensitivity to Factive or other quinolones.
Patients with a history of Factive or other quinolone-associated tendonitis and tendon rupture.
Children or growing adolescents under 18 years of age.
Pregnant or lactating women.
Warnings
Warning statement according to the Notification of the Ministry of Public Health for oral fluroquinolones: Known hypersensitivity to Factive or other quinolones.
Avoid to use in pregnant or lactating women.
Call a healthcare provider right away at the first signs or symptoms of rash, muscular pain, swelling or inflammation in a tendon area. These could be symptoms of tendinitis or tendon rupture. Stop taking fluoroquinolone until a healthcare provider has determined that the patient does not have tendinitis or a tendon rupture.
Patients might have experience in nephrotoxicity and hepatotoxicity while receiving therapy with quinolones.
Should be used with caution in patients with existing or suspected central nervous system diseases e.g., severe cerebral arteriosclerosis (risk of convulsion).
Patients can experience Stevens-Johnson syndrome, Toxic Epidermal Necrolysis or Erythema Multiforme while receiving therapy with quinolones. Closely monitor patients' reaction to the drug. If these symptoms occur, drug should be discontinued and appropriate measures instituted.
Hyperglycemia can sometimes occur so closely monitor when exercise drug in diabetic patients.
May cause the increase effect of warfarin while receiving therapy with quinolones.
Special Precautions
Patients with severe renal impairment.
Quinolones may prolong the QT interval in some patients. Factive should be avoided in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorders (hypokalemia or hypomagnesemia), and patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents.
Factive should be used with caution in patients with epilepsy or patients with a history of convulsions (risk of convulsion).
Factive should be used with caution in patients with existing or suspected central nervous system diseases e.g., severe cerebral arteriosclerosis (risk of convulsion).
Quinolones should be used with caution in patients with existing or family history of glucose-6-phosphate dehydrogenase deficiency (rarely haemolytic reactions may be developed during therapy).
Use In Pregnancy & Lactation
Gemifloxacin treatment during organogenesis caused fetal growth retardation in mice (oral dosing at 450 mg/kg/day), rats (oral dosing at 750 mg/kg/day) and rabbits (IV dosing at 40 mg/kg/day). Treatment of pregnant rats at 750 mg/kg/day caused fetal brain and ocular malformations (unilateral microphthalmia, anophthalmia, and dome shaped head) in the presence of maternal toxicity.
Factive should not be used in pregnant women because the safety of Factive in pregnant women has not been established.
Stop breast-feeding during the administration of Factive because animal studies have shown gemifloxacin-related material is excreted in the breast milk of rats.
Adverse Reactions
Shock: Anaphylactic shock or anaphylactic reactions may occur rarely. Closely monitor patients' reaction to the drug. If patients experience trouble breathing, decreased blood pressure or dyspnea while receiving Factive, the drug should be discontinued immediately and appropriate measures instituted.
Central Nervous System: Quinolone family of antibiotics may lead to increase in intracranial pressure and CNS stimulation which eventually lead to tremor, anxiety, lightheadedness, confusion, hallucination, paranoia, depression, nightmares, insomnia or rarely suicidal thoughts or acts. Dizziness can occur occasionally, tremor rarely and headache might also occur.
Gastrointestinal: Rarely, patients can develop fatal pseudomembraneous colitis or colitis associated with bloody stool. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including FACTIVE. If the patient experiences stomach cramps, frequent diarrhea or symptoms of colitis after administration of FACTIVE, tests to confirm CDAD should be conducted and appropriate measures instituted. Abdominal pains, vomiting, constipation, dry mouth, dyspepsia, flatulence, gastritis, and hyperglycemia can sometimes occur, gastroenteritis rarely, and anorexia and diarrrhea might also occur.
Hepatic: Patients can develop asymptomatic transient elevation of liver enzyme (AST/ALT) occasionally, bilirubinemia, γ-GTP elevation and increased GGT rarely.
Hypersensitive Reaction: Rash, hives and itching can occur occasionally, photosensitivity rarely. Diffuse maculopapular or erythematous skin rash was reported in clinical trials with Factive. The incidences of rash were observed approximately after 7 days since the initiation of the treatment and eighty percent of rashes resolved within 14 days. The rashes were generally considered to be mild to moderate reversible hypersensitive reaction (type IV). Factive should be discontinued immediately at the appearance of any sign of an immediate type I hypersensitivity skin rash or any other manifestation of a hypersensitivity reaction.
Dermatologic: Patients can experience Stevens-Johnson syndrome and Lyell's Syndrome while receiving therapy with quinolones. Closely monitor patients' reaction to the drug. If these symptoms occur, FACTIVE should be discontinued and appropriate measures instituted. Patients can develop dermatitis, fungal infection of reproductive organs, genital pruritus and vaginitis occasionally, eczema rarely.
Musculoskeletal: Arthralgia can occur, tendonitis and increased creatine phosphokinase occasionally, and back pain and leg cramps rarely.
Hematology: Decreased and increased platelets and decreased leucopenia can occur occasionally, anemia, eosinophilia and granulocytopenia rarely.
Respiratory: Trouble breathing and pneumonia can occur rarely.
Peripheral Nervous System: Quinolones may rarely cause sensorimotor axonal polyneuropathy or affect axons which results in paresthesia, hypoesthesia, dysesthesias or weakness.
Other: Fungal overgrowth, fatigue and taste perversion can occur occasionally, hot flashes, flushing, restlessness, pharyngitis and abnormal vision rarely.
Drug Interactions
Gemifloxacin absorption is significantly reduced and its efficacy may be lowered when aluminium- and/or magnesium-containing antacids, ferrous sulphate (iron), calcium preparation, multivitamin preparation containing zinc or iron are concomitantly administered. FACTIVE should not be taken within 3 hours before and after taking these agents.
Didanosin should not be taken within 3 hours before or after taking FACTIVE.
Sucralfate and calcium carbonate should not be taken within 2 hours before or after taking FACTIVE.
No clinically significant interactions have been observed when gemifloxacin was co-administered with omeprazole, theophylline, digoxin, warfarin, oral contraceptives, or cimetidine.
FACTIVE had no significant effect on the anticoagulant effect of warfarin in healthy subjects on stable warfarin therapy. However, increases in the INR (International Normalized Ratio), or PT (prothrombin time), and/or clinical episodes of bleeding in patients have been noted with the use of quinolones, including FACTIVE, and warfarin, or its derivatives.
Storage
Store below 30°C in tight container.
Shelf-Life:
36 months.
MIMS Class
ATC Classification
J01MA15 - gemifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 320 mg (white to off-white, oval-shaped, with breaklines on both sides and debossed with LG 320 on both sides) x 5's.
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